Thorsten Orlikowsky

Neonatal non-contact respiratory monitoring based on real-time infrared thermography

BackgroundMonitoring of vital parameters is an important topic in neonatal daily care. Progress in computational intelligence and medical sensors has facilitated the development of smart bedside monitors that can integrate multiple parameters into a single monitoring system. This paper describes non-contact monitoring of neonatal vital signals based on infrared thermography as a new biomedical engineering application. One signal of clinical interest is the spontaneous respiration rate of the neonate. It will be shown that the respiration rate of neonates can be monitored based on analysis of the anterior naris (nostrils) temperature profile associated with the inspiration and expiration phases successively.ObjectiveThe aim of this study is to develop and investigate a new non-contact respiration monitoring modality for neonatal intensive care unit (NICU) using infrared thermography imaging. This development includes subsequent image processing (region of interest (ROI) detection) and optimization. Moreover, it includes further optimization of this non-contact respiration monitoring to be considered as physiological measurement inside NICU wards.ResultsContinuous wavelet transformation based on Debauches wavelet function was applied to detect the breathing signal within an image stream. Respiration was successfully monitored based on a 0.3°C to 0.5°C temperature difference between the inspiration and expiration phases.ConclusionsAlthough this method has been applied to adults before, this is the first time it was used in a newborn infant population inside the neonatal intensive care unit (NICU). The promising results suggest to include this technology into advanced NICU monitors.

Maternal and fetal cord blood lipids in intrauterine growth restriction.

Abstract Aim: Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses. Methods: Umbilical cord serum lipids and oxidative modified, low-density lipoprotein (oxLDL) concentrations were measured by colorimetric enzymatic measurements, or by ELISA. Values of IUGR (n=36) and constitutionally small for gestational age neonates (SGA, n=22) were compared with those of healthy, adequate for gestational age, born neonates (CN, n=97). SAS-statistic software was used and two-way ANOVA was adjusted for gestational age at delivery. Results: Fetal high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) concentrations were found to be lower in the IUGR compared to the CN and SGA groups (HDL-C: P<0.001, TC: P<0.01). Atherogenic indices, including the oxLDL/LDL-C ratio, were increased in the IUGR compared to the CN group (oxLDL/LDL-C ratio: P<0.001). Conclusion: Our results support the hypothesis of a disturbed cholesterol supply in IUGR fetuses. Born SGA has been shown to be a risk factor for developing cardiovascular disease later in life. Since HDL-C has anti-inflammatory properties, a reduced HDL-C during fetal development, and an increase in atherogenic indices, might provide a link to this observation in IUGR fetuses.

Impact of Skin to Skin Care, Prone and Supine Positioning on Cardiorespiratory Parameters and Thermoregulation in Premature Infants

Background: Skin to skin care (SSC), prone (PP) and supine (SP) positions are standard positions in daily care for premature infants. Their influence on cardiorespiratory parameters and thermoregulation is discussed controversially. Objectives: We compared SSC with PP, the recommended position for preterm infants, and SP, the safest position for term infants, and tested the hypothesis that SSC has no impact on cardiorespiratory parameters and thermoregulation. Methods: In 18 spontaneously breathing premature infants [median gestational 28 weeks (24–32); chronological age 36 days (7–64), and weight 1,543 g (750–2,100)], heart and respiratory rate, breathing pattern, episodes of desaturation (<85 but ≧80 and <80%), oxygen saturation and rectal temperature were analyzed with polygraphy (Alice 3® and 3.5®) in a 6-hour measuring cycle of three subsequent series (120 min each in SP, SSC and PP) and compared (Wilcoxon test). Results: During SSC, we found no increase in apneic attacks and bradycardic episodes and no difference in respiratory rate, breathing pattern, oxygen saturation, episodes and duration of desaturation compared to SP and PP. Episodes of desaturation <85 but ≧80 and <80% were more frequent in SP compared to PP (p = 0.0421 and p = 0.0319). Heart rate increased in SSC and PP compared to SP (154.86 bpm, SD 11.55, and 153.33 bpm, SD 15.95 vs. 150.25 bpm, SD 14.64; p = 0.0013 and p = 0.0346). Temperature level was not significantly higher during SSC and PP compared to SP except a rise between the start and the end of the 6-hour measuring cycle (37.05°C, SD 0.2 vs. 37.30°C, SD 0.3; p = 0.0436). Conclusion: We found no significant SSC-mediated changes in quality and quantity of desaturations and in body temperature compared to PP in preterm infants.

Monocytes derived from humanized neonatal NOD/SCID/IL2Rγnull mice are phenotypically immature and exhibit functional impairments

Trials of immune-modulating drugs in septic patients have mostly failed to demonstrate clinical efficacy. Thus, we sought to generate a surrogate model of myelomonocytic lineage differentiation that would potentially allow sepsis induction and preclinical testing of anti-inflammatory drugs. Comparing transplantation of cord blood-derived stem cells in neonatal NOD/SCID/IL2Rγ(null) (neonatal huNSG) mice with transplantation of adult peripheral mobilized stem cells into adult NSG (adult huNSG) recipients, we demonstrate that myelomonocytic lineage differentiation in neonatal huNSG mice is retarded and monocytes are phenotypically immature with respect to HLA-DR expression and the emergence of CD80(+)CD86(+) monocytes. Functionally, neonatal huNSG mice were less sensitive toward interferon-γ-induced upregulation of CD86 and exhibited a reduced T-cell stimulating capacity when compared with adult huNSG mice, whereas the phagocytic activity and the ability for cytokine secretion were mature. However, comparison of these data with data obtained from human neonates indicate that absence of the CD80(+)CD86(+) population and the reduced T-cell stimulating capacity of neonatal huNSG monocytes resemble functional immaturities observed in human neonatal monocytes. Thus, these two mouse models might well serve as 2 independent surrogate models for studying the neonatal myelomonocytic lineage differentiation or for testing the efficacy of immunomodulatory drugs on functionally mature monocytes.

NeonatOx: a pumpless extracorporeal lung support for premature neonates.

Gas exchange in premature neonates is regularly impaired by structural and functional immaturity of the lung. Mechanical ventilation, which is vitally important to sustain oxygenation and CO(2) elimination, causes, at the same time, mechanical and inflammatory destruction of lung tissue. To date, extracorporeal oxygenation is not a treatment option, one reason among others being the size of available oxygenators and cannulas. We hypothesized that a substantial improvement in gas exchange can be achieved by maintenance of the fetal cardiopulmonary bypass and interposition of a suitable passively driven (arteriovenous) membrane oxygenator. In close cooperation between engineers and neonatologists, we developed a miniaturized oxygenator and adapted cannulas to be used as a pumpless extracorporeal lung support that is connected to the circulation via cannulation of the umbilical cord vessels. First in vitro and in vivo studies show promising results. We regard this as one step on the way to clinical application of the artificial placenta.

Infrared thermography for detailed registration of thermoregulation in premature infants.

Abstract Objective: To evaluate skin temperature by using different positions with non-contact infrared thermography (IRT) in multiple body areas of preterm infants for detailed information about temperature regulation and distribution. Methods: The temperature of ten premature infants (median: 27 weeks; age 36 days; weight 1322 g) was determined via IRT (leg, back, arm, head, upper abdomen; diameter 1 cm, scale 0.00°C), and comparison was made with two conventional sensors. There were measurements of 10 min each: first incubator phase (I1), standardized skin-to-skin care (SSC) at the beginning (SSC1), after 90 min (SSC2), and then there was a second incubator phase (I2). Results: From I1 to SSC1, patients cooled down (max. 0.62°C; both methods). From SSC1 to SSC2 temperature on central areas (abdomen, back) was maintained but rose distinctively on the head and leg (P<0.05). In the incubator (I2), temperature niveau in all IRT-areas was significantly lower than before SSC. Conclusion: Via IRT, it is possible to detect fluctuations in temperature of premature infants. The cooling in I2 after SSC should be taken into account before routine daily care.

Diagnostic Value of an Interleukin-6 Bedside Test in Term and Preterm Neonates at the Time of Clinical Suspicion of Early- and Late-Onset Bacterial Infection

Background: For quick detection or exclusion of neonatal early-onset bacterial infection (EOBI) or late-onset bacterial infection (LOBI), interleukin (IL)-6 is used. Its clinical use is sometimes limited due to prolonged recall times. Therefore, an IL-6 bedside test was established. Objective: To compare the diagnostic value of plasma IL-6 and an IL-6 bedside test at the time of clinical suspicion in the course of EOBI and LOBI. Methods: Eighteen term (mean gestational age 40.2 weeks, SD 1.3) and 88 preterm (mean gestational age 30.1 weeks, SD 4.2) neonates with clinical and serological signs of bacterial infection were analysed. Eight had an EOBI, and 24 had a LOBI, of whom 13 were blood culture positive. Twelve term and 62 preterm neonates with risk factors but without proven EOBI/LOBI served as a non-infected group. Results: At the time of clinical suspicion, the sensitivity of the IL-6 bedside test in comparison to plasma IL-6 was 69 versus 75% (p = 0.7744, McNemar’s test), and specificity was 77 versus 81% (p = 0.6476, McNemar’s test; cutoff level 50 ng/l). For LOBI, both the sensitivity (75%) and specificity (82%) of the bedside test exceeded values calculated for EOBI (sensitivity 50%, specificity 75%). Conclusion: No significant difference between the bedside and established plasma IL-6 test was detected for LOBI. For detection of EOBI, the bedside test was not sensitive enough. Larger studies are needed to verify our findings before IL-6 bedside tests can be recommended routinely.

Fifty Years of Work on the Artificial Placenta: Milestones in the History of Extracorporeal Support of the Premature Newborn

The concept of an artificial placenta has been pursued in experimental research since the early 1960s. The principle has yet to be successfully implemented in neonatal care despite the constant evolution in extracorporeal life support technology and advancements in neonatal intensive care in general. For more than three decades, the physical dimensions of the required equipment necessitated pump-driven circuits; however, recent advances in oxygenator technology have allowed exploration of the simpler and physiologically preferable concept of pumpless arteriovenous oxygenation. We expect that further miniaturization of the extracorporeal circuit will allow the implementation of the concept into clinical application as an assist device. To this end, NeonatOx (Fig. 1), a custom-made miniaturized oxygenator with a filling volume of 20 mL, designed by our own group, has been successfully implemented with a preterm lamb model of less than 2000 g body weight as an assist device. We provide an overview of milestones in the history of extracorporeal membrane oxygenation of the preterm newborn juxtaposed against current and future technological advancements. Key limitations, which need to be addressed in order to make mechanical gas exchange a clinical treatment option of prematurity-related lung failure, are also identified.

Miniaturization: the clue to clinical application of the artificial placenta.

The artificial placenta as a fascinating treatment alternative for neonatal lung failure has been the subject of clinical research for over 50 years. Pumpless systems have been in use since 1986. However, inappropriate dimensioning of commercially available oxygenators has wasted some of the theoretical advantages of this concept. Disproportional shunt fractions can cause congestive heart failure. Blood priming of large oxygenators and circuits dilutes fetal hemoglobin (as the superior oxygen carrier), is potentially infectious, and causes inflammatory reactions. Flow demands of large extracorporeal circuits require cannula sizes that are not appropriate for use in preterm infants. NeonatOx, a tailored low-volume oxygenator for this purpose, has proven the feasibility of this principle before. We now report the advances in biological performance of a refined version of this specialized oxygenator.

Influence of Smoking and Alcohol during Pregnancy on Outcome of VLBW Infants

BACKGROUND Nicotine and alcohol consumption have been associated with premature delivery and adverse neonatal outcome. We wanted to analyze the influence of self-reported nicotine and alcohol consumption on outcome of VLBW infants. MATERIAL AND METHODS In an ongoing multicenter study 2475 parents of former very low birth weight (VLBW) infants born between January 2009 and December 2011 answered questionnaires about maternal smoking habits and alcohol consumption during pregnancy. 2463 (99.5%) completed questions on alcohol consumption and 2462 (99.5%) on smoking habits. These infants were stratified to reported maternal smoking and alcohol consumption during pregnancy. We compared the reasons for premature delivery, neonatal outcome and parental reports on bronchitis during the first year of life, as well as growth and development at age 2 years to pregnancy exposure. RESULTS In nicotine exposed infants intrauterine growth restriction (31 vs. 21%, p<0.01), a birth weight below the 10th percentile (26 vs. 17%, p<0.01) and placenta abruption (9.2 vs. 5.8%, p<0.05) was seen more often. Premature rupture of membranes (24 vs. 30%, p<0.05) or HELLP syndrome (6 vs. 11%, p<0.01) was less frequent. A birth weight below the 3rd percentile was seen more frequently in mothers with reported alcohol consumption (13 vs. 6%, p<0.05). We noted an increased rate of BPD and ROP if mothers reported smoking during pregnancy (p<0.05). Growth parameters and scores on Bayley Sscales of infant development at age 2 years did not differ. CONCLUSION Smoking during pregnancy results in a high rate of growth restricted VLBW infants. Prenatal exposition to nicotine seems to increase postnatal complications such as BPD und ROP.